Abstract: The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.

Abstract: The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.

Abstract: Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.

Abstract: Provided is a method of assaying for an analyte, including combining a test sample having the analyte, with a calibration sample having at least two different aliquots of the analyte, each aliquot having a different known quantity of the analyte. The test sample and each aliquot are differentially labeled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry. The method further includes determining by mass spectrometry the quantity of analyte in the test sample and in each aliquot, and calibrating the quantity of analyte in the test sample against known and determined quantities of analytes in the aliquots.

Abstract: The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl)carbonyl]indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof; and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.

Abstract: Alzheimer's disease (AD) is the most common type of dementia in aging adults with the number of people living with AD projected to increase, making the search for treatments and tools to diagnose and measure disease progression increasingly urgent. In particular, ideal biomarkers for diagnosis of AD should not only have high specificity for disease versus non-disease and high sensitivity for distinguishing between disease types but also should be able to detect changes at a very early stage of the disease. Using microglia activation as an early event of AD's onset, the present inventors have identified a panel of biomarkers in CSF which has the potential to diagnose, stage and determine the likelihood of developing AD.

Abstract: The present invention provides a method for labelling one or more analytes in a sample, the method comprising: a) contacting the sample with one or more bifunctional linker reagents having the general formula Re1-L1-Re2, wherein Re1 is a first reactive group, L1 is a linker moiety and Re2 is a second reactive group, wherein Re1 reacts with an analyte to form a modified analyte; and b) contacting the sample with one or more mass labels, wherein Re2 of the bifunctional linker attached to the analyte reacts with a mass label to form a labelled analyte, wherein each mass label is relatable to an analyte by mass spectrometry.

Abstract: The present invention relates to a set of two or more mass labels. Each mass label comprises: X-L-M-Re; X is a reporter moiety having exact mass; L is a bond cleavable by collision in a mass spectrometer; M is a mass modifier; Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte. Each mass label in the set has the same integer mass; wherein the set comprises two or more subsets of mass labels, each subset comprising one or more mass labels; wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets; each mass label is distinguishable by mass spectrometry.

Abstract: The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.

Abstract: The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.

Abstract: Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.

Abstract: The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl)carbonyl]indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof; and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.

Abstract: The invention relates to panels of biomarkers including proteins phosphatase 1 regulatory subunit 14A and/or 2?,3?-cyclic-nucleotide 3?-phosphodiesterase and/or phosphorylated tau or fragments thereof and methods using thereof for diagnosing, staging, treating and assessing the response of a treatment for a neurocognitive disorder characterised by tau toxicity, in particular for Alzheimer's disease. The present invention shows that the biomarkers disclosed herein are elevated in the brain of subjects with an advanced stage of a neurocognitive disorder (Braak stage V/VI) and/or are regulated in the CSF of AD subjects in comparison to cognitively affected non-AD controls; and/or regulated in response to two casein kinase 1 delta inhibitors.

Abstract: Alzheimer's disease (AD) is the most common type of dementia in aging adults with the number of people living with AD projected to increase, making the search for treatments and tools to diagnose and measure disease progression increasingly urgent. In particular, ideal biomarkers for diagnosis of AD should not only have high specificity for disease versus non-disease and high sensitivity for distinguishing between disease types but also should be able to detect changes at a very early stage of the disease. Using microglia activation as an early event of AD's onset, the present inventors have identified a panel of biomarkers in CSF which has the potential to diagnose, stage and determine the likelihood of developing AD.

Abstract: The invention relates to pharmaceutical compositions having casein kinase 1 delta (CK1?) inhibitors and to the use of the inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.

Abstract: The invention relates to pharmaceutical compositions having casein kinase 1 delta (CK1?) inhibitors and to the use of the inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.

Abstract: Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders.

Abstract: The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.

Abstract: Provided is a method of assaying for an analyte, including combining a test sample having the analyte, with a calibration sample having at least two different aliquots of the analyte, each aliquot having a different known quantity of the analyte. The test sample and each aliquot are differentially labeled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry. The method further includes determining by mass spectrometry the quantity of analyte in the test sample and in each aliquot, and calibrating the quantity of analyte in the test sample against known and determined quantities of analytes in the aliquots.

Abstract: The invention relates to pharmaceutical compositions comprising casein kinase 1 delta (CK1?) and to the use of said inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.